Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
Org Lett. 2022 Jul 22;24(28):5176-5180. doi: 10.1021/acs.orglett.2c02012. Epub 2022 Jul 11.
Forging new C(sp)-C(sp) bonds to central positions within a peptide backbone is critical for the development of new therapeutics and chemical probes. Currently, there are no methods for decarboxylating Asp and Glu side chains solid-phase photochemically or using such radicals to form peptide macrocycles. Herein, electron-donor-acceptor complexes between Hantzsch ester and on-resin peptide -hydroxyphthalimide radical precursors are used to access these radicals, demonstrated with two-carbon homologations and homologation cyclizations of Atosiban and RGDf.
在肽主链的中心位置形成新的 C(sp)-C(sp) 键对于新疗法和化学探针的开发至关重要。目前，还没有方法可以通过固相光化学脱羧 Asp 和 Glu 侧链，或者使用这些自由基来形成肽大环。在此，通过 Hantzsch 酯与树脂上的肽 -羟基邻苯二甲酰亚胺自由基前体之间的给体-受体络合物来获得这些自由基，通过阿托西班和 RGDf 的两碳同系化和同系化环化来证明这一点。
